B6-Pnpla3*I148M Mouse

The PNPLA3 gene encodes a triglyceride lipase that mobilizes polyunsaturated fatty acids and promotes the secretion of large very-low-density lipoproteins by the liver. It is mainly expressed in the liver, adipose tissue, and hepatic stellate cells, participating in lipid metabolism, especially triglyceride hydrolysis and lipid droplet remodeling. Its I148M mutation is significantly associated with metabolism-associated fatty liver disease (MASLD), alcoholic liver disease, and liver fibrosis. The I148M mutant, as an inhibitor of PNPLA2/ATGL-mediated lipolysis, disrupts lipid droplet metabolism and promotes hepatic steatosis ^[1]. PNPLA3 is highly upregulated in a high-carbohydrate diet, and the I148M variant exacerbates the harmful effects of a high-sucrose diet on non-alcoholic fatty liver. Targeted degradation of PNPLA3 I148M through means such as shRNA-mediated gene knockout or siRNA can reduce protein abundance and alleviate steatosis ^[2-3].

B6-Pnpla3*I148M mice are obtained by introducing the I148M mutation into the mouse Pnpla3 gene using gene editing technology. Homozygous B6-Pnpla3*I148M mice are viable and fertile. This model can be used for research on the disease mechanisms and treatment methods of metabolism-associated fatty liver disease (MASLD), alcoholic liver disease, and liver fibrosis.